The authors of a new study, led by Queen Mary University of London, say spironolactone, or amiloride if spironolactone is not tolerated, should be considered as first-line treatment for resistant hypertension in addition to background treatments with other antihypertensive drugs.
The PATHWAY-2 study, carried out by the same team, has previously reported that spironolactone reduced BP substantially more than conventional antihypertensive drugs in patients with resistant hypertension.
PATHWAY-2 was a randomised, double-blind crossover trial carried out at 14 UK primary and secondary care sites and incorporating 314 patients with resistant hypertension. Patients received 12 weeks of once-daily placebo, spironolactone 25-50 mg, bisoprolol 5-10 mg and doxazosin 4-8 mg.
This latest research, published in the Lancet Diabetes & Endocrinology, carried out 3 PATHWAY-2 substudies. Substudy 1 assessed plasma aldosterone, renin, and aldosterone-to-renin ratio (ARR) as predictors of home systolic BP (SBP), and estimated prevalence of primary aldosteronism. Substudy 2 assessed the effects of each drug on thoracic fluid, cardiac and stroke indices, and systemic vascular resistance. Substudy 3 assessed the effect of once-daily amiloride 10-20 mg on SBP.
The researchers found that ARR and plasma renin predicted SBP reduction with spironolactone. Thoracic fluid content was reduced by 6.8% with spironolactone, but not with other treatments. Amiloride 10 mg reduced SBP by 20.4 mmHg vs 18.3 mmHg with spironolactone 25 mg.
No serious adverse events were recorded. Mean plasma potassium concentrations increased from 4.02 mmol/L on placebo to 4.50 mmol/L on amiloride.
The authors say the results suggest that resistant hypertension is commonly a salt-retaining state. They concluded that spironolactone overcomes the salt retention and resistance to treatment. Amiloride seems to be as effective as spironolactone and can be used as an alternative when spironolactone is not tolerated.